Combination of doxorubicin and sulforaphane for reversing doxorubicin-resistant phenotype in mouse fibroblasts with p53Ser220 mutation.
Ann N Y Acad Sci
; 1095: 62-9, 2007 Jan.
Article
in En
| MEDLINE
| ID: mdl-17404018
ABSTRACT
Chemoresistance in cancer therapy is a multifactorial process, which includes alterations in drug accumulation, increased activity of gluthatione S-transferases, loss of function, and mutations of p53, etc. One strategy for reversing chemoresistance is the use of chemopreventive agents alongside standard chemotherapeutic protocols. Sulforaphane is one of the most promising chemopreventive agents. Sulforaphane inhibits cell proliferation and induces apoptosis in different tumor cell lines. Its proapoptotic potential could make it effective either alone or in combination with other therapeutic strategies in reversing chemoresistance. We investigated the effects of sulforaphane on mouse fibroblasts bearing a different p53 status (wild-type, knockout, mutated) for understanding whether its activity is prevented by a mutated p53 status. p53-knockout fibroblasts from newborn mice transfected with the p53(Ser220) mutation, observed in different human cancers, were used as a model of mutated p53 status. Moreover, since p53(Ser220) mutation fibroblasts showed a doxorubicin-resistant phenotype, we treated the cells with a combination of doxorubicin plus sulforaphane. Taken together, our results suggest that a mutated p53 status did not prevent the induction of apoptosis by sulforaphane and that sulforaphane was able to reverse the resistance to doxorubicin. The association of sulforaphane-doxorubicin may therefore allow doxorubicin to be administered at lower doses, thereby reducing its potential toxicity.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thiocyanates
/
Antineoplastic Combined Chemotherapy Protocols
/
Doxorubicin
/
Tumor Suppressor Protein p53
/
Anticarcinogenic Agents
/
Drug Resistance, Neoplasm
/
Fibroblasts
/
Antibiotics, Antineoplastic
Type of study:
Guideline
Limits:
Animals
/
Humans
Language:
En
Journal:
Ann N Y Acad Sci
Year:
2007
Type:
Article
Affiliation country:
Italy